Li Ping, Chen Yuhui, Song Jieyun, Yan Lailai, Tang Tiantian, Wang Rui, Fan Xiuqin, Zhao Yurong, Qi Kemin
Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institution, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nan-li-shi Road, Xicheng District, Beijing, 100045, China.
Department of Obstetrics and Gynecology, Fuxing Hospital, Capital Medical University, No. 20 Fu-xing-men-wai Street, Xicheng District, Beijing, 100038, China.
Nutr Metab (Lond). 2022 Jul 23;19(1):48. doi: 10.1186/s12986-022-00683-3.
The single nucleotide polymorphisms (SNPs) in the fatty acid desaturases and elongases might associate with the endogenous synthesis of polyunsaturated fatty acids (PUFAs). However, the related epidemiological evidence is still conflicting. So we aimed to clearly evaluate the interactions between maternal DHA-rich n-3 PUFAs supplementation and the known 26 SNPs on the profiles of PUFAs in the colostrum using a Chinese birth cohort.
Totally, 1050 healthy mother-infant pairs were enrolled in this study at gestational 6-8 weeks when they established their pregnancy files at Fuxing Hospital affiliated to Capital Medical University in Beijing from January to December 2018. Meanwhile, their venous blood samples were obtained for DNA extraction to detect the genotypes of SNPs in the Fads1, Fads2, Fads3, Elovl2 and Elovl5 using the Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry. Then the colostrum samples were collected to determine the profiles of PUFAs by gas chromatography.
Maternal DHA-rich n-3 PUFAs supplementation from the early and middle pregnancy could reduce the infant BMI at birth, and impact the profiles of PUFAs in the colostrum, as higher n-3 PUFAs (EPA, DHA, DHA/ALA and DHA/EPA), lower n-6 PUFAs (AA and AA/LA) and ∑-6/n-3ΣPUFAs. Moreover, there were significant correlations between multiple SNPs and the profiles of n-6 PUFAs (rs76996928 for LA, rs174550, rs174553 and rs174609 for AA, rs174550 and rs76996928 for AA/LA) and n-3 PUFAs in the colostrum (rs174448, rs174537, rs174550, rs174553, rs174598, rs3168072, rs174455 and rs174464 for ALA, rs174550, rs174553 and rs174598 for EPA, rs174455 and rs174464 for DHA, rs174448 and rs3168072 for DHA/EPA) using the multiple linear regressions by adjusting the maternal age, gestational week, mode of delivery, infant sex and BMI at birth, and all these above significant SNPs had the cumulative effects on the profiles of PUFAs. Furthermore, the pairwise comparisons also showed the meaningful interactions between maternal DHA-rich n-3 PUFAs supplementation and related genotypes of SNPs (rs76996928 for LA, rs174598 for EPA, rs174448 for DHA and DHA/EPA) on the contents of PUFAs in the colostrum.
Results from this birth cohort study proved that the pregnant women with the following SNPs such as Fads3 rs174455 T, Fads3 rs174464 A and Fads1 rs174448 G alleles should pay more attention on their exogenous DHA supplementation from the early and middle pregnancy for the blocked endogenous synthesis.
This study was approved by the Ethics Committee of Beijing Pediatric Research Institution, Beijing Children's Hospital affiliated to Capital Medical University (2016-08), which was also registered at the website of http://www.chictr.org.cn/showproj.aspx?proj=4673 (No: ChiCTR-OCH-14004900).
脂肪酸去饱和酶和延长酶中的单核苷酸多态性(SNP)可能与多不饱和脂肪酸(PUFA)的内源性合成有关。然而,相关的流行病学证据仍存在冲突。因此,我们旨在利用一个中国出生队列,明确评估孕期补充富含二十二碳六烯酸(DHA)的n-3多不饱和脂肪酸与已知的26个SNP之间对初乳中多不饱和脂肪酸谱的相互作用。
2018年1月至12月,在北京首都医科大学附属复兴医院建立妊娠档案时,共纳入1050对健康母婴,孕周为6-8周。同时,采集她们的静脉血样本进行DNA提取,采用基质辅助激光解吸电离飞行时间质谱法检测脂肪酸去饱和酶1(Fads1)、脂肪酸去饱和酶2(Fads2)、脂肪酸去饱和酶3(Fads3)、脂肪酸延长酶2(Elovl2)和脂肪酸延长酶5(Elovl5)中SNP的基因型。然后收集初乳样本,用气相色谱法测定多不饱和脂肪酸谱。
孕早期和中期补充富含DHA的n-3多不饱和脂肪酸可降低婴儿出生时的体重指数,并影响初乳中多不饱和脂肪酸谱,即n-3多不饱和脂肪酸(二十碳五烯酸、DHA、DHA/α-亚麻酸和DHA/二十碳五烯酸)含量升高,n-6多不饱和脂肪酸(花生四烯酸和花生四烯酸/亚油酸)含量降低,以及∑-6/n-3∑多不饱和脂肪酸降低。此外,通过调整产妇年龄、孕周、分娩方式、婴儿性别和出生时体重指数进行多元线性回归分析,发现多个SNP与初乳中n-6多不饱和脂肪酸谱(亚油酸的rs76996928、花生四烯酸的rs174550、rs174553和rs174609、花生四烯酸/亚油酸的rs174550和rs76996928)和n-3多不饱和脂肪酸谱(α-亚麻酸的rs174448、rs174537、rs174550、rs174553、rs174598、rs3168072、rs174455和rs174464、二十碳五烯酸的rs174550、rs174553和rs174598、DHA的rs174455和rs174464、DHA/二十碳五烯酸的rs174448和rs3168072)之间存在显著相关性,上述所有显著的SNP对多不饱和脂肪酸谱均有累积效应。此外,两两比较还显示,孕期补充富含DHA的n-3多不饱和脂肪酸与SNP的相关基因型(亚油酸的rs76996928、二十碳五烯酸的rs174598、DHA和DHA/二十碳五烯酸的rs174448)之间对初乳中多不饱和脂肪酸含量存在有意义的相互作用。
本出生队列研究结果证明,携带脂肪酸去饱和酶3 rs174455 T、脂肪酸去饱和酶3 rs174464 A和脂肪酸去饱和酶1 rs174448 G等SNP的孕妇,由于内源性合成受阻,应在孕早期和中期更加关注外源性DHA的补充。
本研究经首都医科大学附属北京儿童医院北京儿科研究所伦理委员会批准(2016-08),并在http://www.chictr.org.cn/showproj.aspx?proj=4673网站注册(编号:ChiCTR-OCH-14004900)。